tbuckley/cabot-search huggingface dataset:
How pandemic publishing struck a blow to the visibility of women’s expertise
Authors: Jocalyn Clark
Journal: BMJ (2023)

The biases in scientific publishing during the pandemic damaged women's visibility, recognition, and career advancement, reports Jocalyn Clark Jocalyn Clark international editorBefore covid-19, Reshma Jagsi had a thriving clinical and research career.As a full time physician and deputy department chair of radiation oncology at the University of Michigan, USA, she was ascending the leadership ladder before the world around her went into lockdown."Everything was an emergency, and [all my colleagues were] working around the clock out of a sense of need, because the house was on fire," she says.It felt as though "I was drowning.
An ALARMINg Type 2 Response in Cystic Fibrosis—The Key to Understanding ABPA?
Authors: Christine M. Bojanowski, Jacob P. Bitoun, Jay K. Kolls
Journal: American Journal of Respiratory and Critical Care Medicine (2023)

"An ALARMINg Type 2 Response in Cystic Fibrosis – The Key to Understanding ABPA?." American Journal of Respiratory and Critical Care Medicine, 0(ja), pp. –
Mandatory vs. optional split-dose bowel preparation for morning colonoscopies: a pragmatic noninferiority randomized controlled trial
Authors: Casandra Dolovich, Claire Unruh, Dana C. Moffatt, Carrie Loewen, Brennan Kaita, Alan N. Barkun, Myriam Martel, Harminder Singh
Journal: Endoscopy (2023)

BACKGROUND : We compared the effectiveness of optional split-dose bowel preparation (SDBP) with mandatory SDBP for morning colonoscopies in usual clinical practice. METHODS : Adult patients undergoing outpatient early morning (8:00 AM-10:30 PM) and late morning (10:30 AM-12:00 PM) colonoscopies were included. Written bowel preparation instructions were provided based on randomization: one group were instructed to take their bowel preparation (4 L polyethylene glycol solution) as a split dose (mandatory), while the comparator group was allowed the choice of SDBP or single-dose bowel preparation administered entirely on the day before (optional). The primary end point, using noninferiority hypothesis testing with a 5 % margin, was adequate bowel cleanliness measured by the Boston Bowel Preparation Scale (BBPS) and defined by a BBPS score ≥ 6. RESULTS : Among 770 randomized patients with complete data, there were 267 mandatory SDBP and 265 optional SDBP patients for early morning colonoscopies, and 120 mandatory SDBP and 118 optional SDBP patients for late morning colonoscopies. Optional SDBP was inferior to mandatory SDBP, with a lower proportion of adequate BBPS cleanliness for early morning colonoscopies (78.9 % vs. 89.9 %; absolute risk difference [aRD] 11.0 %, 95 %CI 5.9 % to 16.1 %), but was not statistically different for late morning colonoscopies (76.3 % vs. 83.3 %; aRD 7.1 %, 95 %CI -1.5 % to 15.5 %). CONCLUSIONS : Optional SDBP is inferior to mandatory SDBP in providing adequate bowel preparation quality for early morning colonoscopies (8:00 AM-10:30 AM), and probably inferior for late morning colonoscopies (10:30 AM-12:00 PM).
Two individuals with potential monkeypox virus reinfection
Authors: Angelo Roberto Raccagni, Diana Canetti, Davide Mileto, Andrea Marco Tamburini, Caterina Candela, Luca Albarello, Fiorenza Bracchitta, Alessandro Mancon, Valeria Micheli, Maria Rita Gismondo, Antonella Castagna, Silvia Nozza
Journal: The Lancet Infectious Diseases (2023)
Risk factors and vectors for SARS-CoV-2 household transmission: a prospective, longitudinal cohort study
Authors: Nieves Derqui, Aleksandra Koycheva, Jie Zhou, Timesh D Pillay, Michael A Crone, Seran Hakki, Joe Fenn, Rhia Kundu, Robert Varro, Emily Conibear, Kieran J Madon, Jack L Barnett, Hamish Houston, Anika Singanayagam, Janakan S Narean, Mica R Tolosa-Wright, Lucy Mosscrop, Carolina Rosadas, Patricia Watber, Charlotte Anderson, Eleanor Parker, Paul S Freemont, Neil M Ferguson, Maria Zambon, Myra O McClure, Richard Tedder, Wendy S Barclay, Jake Dunning, Graham P Taylor, Ajit Lalvani
Journal: The Lancet Microbe (2023)
D–A Structured High‐Performance Photothermal/Photodynamic Thionin‐Synthetic Melanin Nanoparticles for Rapid Bactericidal and Wound Healing Effects
Authors: Wenjing Liu, Yuanyuan Yu, Wei Cheng, Xinyue Wang, Man Zhou, Bo Xu, Ping Wang, Qiang Wang
Journal: Advanced Healthcare Materials (2023)

Abstract Synthesized melanin nanoparticles (SMNPs) are used as advanced photothermal materials. However, their internal structures are complex and disordered, and tuning the photothermal performance of nanoparticles is still a hot spot of concern. This article presents thionin (Th)‐doped SMNPs, namely Th‐SMNPs, which are the first SMNPs formed using the one‐pot polymerization of Th with Levodopa. Th can undergo Michael addition and Schiff base reaction between indole dihydroxy/indolequinone and their oligomers to form donor–acceptor pairs in the structure to modulate the photothermal performance of SMNPs. Structural and spectroscopic analyses and density functional theory simulations further confirm the existence of the donor–acceptor structure. Th‐SMNPs exhibit excellent total photothermal efficiency (34.49%) in the near‐infrared region (808 nm), which is a 60% improvement compared to SMNPs. This allows Th‐SMNPs to exhibit excellent photothermal performance at low power 808 nm laser irradiation. Meanwhile, Th not only enhances the photothermal properties of SMNPs, but also imparts photodynamic effects to SMNPs. Th‐SMNPs can produce 1 O 2 under 660 nm laser irradiation. A dual‐function photothermal and photodynamic textile named Th‐SMNPs@cotton is constructed based on Th‐SMNPs, which can act as a rapid photothermal/photodynamic sterilization and is promising for wound healing treatment of bacterial infections under low‐power dual laser irradiation.
In vivo kinetics of early, non-random methylome and transcriptome changes induced by DNA-hypomethylating treatment in primary AML blasts
Authors: Gabriele Greve, Geoffroy Andrieux, Pascal Schlosser, Nadja Blagitko-Dorfs, Usama-Ur Rehman, Tobias Ma, Dietmar Pfeifer, Gerhard Heil, Andreas Neubauer, Jürgen Krauter, Michael Heuser, Helmut R. Salih, Konstanze Döhner, Hartmut Döhner, Björn Hackanson, Melanie Boerries, Michael Lübbert
Journal: Leukemia (2023)

Abstract Despite routine use of DNA-hypomethylating agents (HMAs) in AML/MDS therapy, their mechanisms of action are not yet unraveled. Pleiotropic effects of HMAs include global methylome and transcriptome changes. We asked whether in blasts and T-cells from AML patients HMA-induced in vivo demethylation and remethylation occur randomly or non-randomly, and whether gene demethylation is associated with gene induction. Peripheral blood AML blasts from patients receiving decitabine (20 mg/m 2 day 1–5) were serially isolated for methylome analyses (days 0, 8 and 15, n = 28) and methylome-plus-transcriptome analyses (days 0 and 8, n = 23), respectively. T-cells were isolated for methylome analyses (days 0 and 8; n = 16). We noted massive, non-random demethylation at day 8, which was variable between patients. In contrast, T-cells disclosed a thousand-fold lesser, random demethylation, indicating selectivity of the demethylation for the malignant blasts. The integrative analysis of DNA demethylation and transcript induction revealed 87 genes displaying a significant inverse correlation, e.g. the tumor suppressor gene IFI27 , whose derepression was validated in two AML cell lines. These results support HMA-induced, non-random early in vivo demethylation events in AML blasts associated with gene induction. Larger patient cohorts are needed to determine whether a demethylation signature may be predictive for response to this treatment.
Super-pangenome analyses highlight genomic diversity and structural variation across wild and cultivated tomato species
Authors: Ning Li, Qiang He, Juan Wang, Baike Wang, Jiantao Zhao, Shaoyong Huang, Tao Yang, Yaping Tang, Shengbao Yang, Patiguli Aisimutuola, Ruiqiang Xu, Jiahui Hu, Chunping Jia, Kai Ma, Zhiqiang Li, Fangling Jiang, Jie Gao, Haiyan Lan, Yongfeng Zhou, Xinyan Zhang, Sanwen Huang, Zhangjun Fei, Huan Wang, Hongbo Li, Qinghui Yu
Journal: Nature Genetics (2023)

Effective utilization of wild relatives is key to overcoming challenges in genetic improvement of cultivated tomato, which has a narrow genetic basis; however, current efforts to decipher high-quality genomes for tomato wild species are insufficient. Here, we report chromosome-scale tomato genomes from nine wild species and two cultivated accessions, representative of Solanum section Lycopersicon, the tomato clade. Together with two previously released genomes, we elucidate the phylogeny of Lycopersicon and construct a section-wide gene repertoire. We reveal the landscape of structural variants and provide entry to the genomic diversity among tomato wild relatives, enabling the discovery of a wild tomato gene with the potential to increase yields of modern cultivated tomatoes. Construction of a graph-based genome enables structural-variant-based genome-wide association studies, identifying numerous signals associated with tomato flavor-related traits and fruit metabolites. The tomato super-pangenome resources will expedite biological studies and breeding of this globally important crop.
A meta-analysis and a functional study support the influence of mtDNA variant m.16519C on the risk of rapid progression of knee osteoarthritis
Authors: Alejandro Durán-Sotuela, Mercedes Fernandez-Moreno, Victoria Suárez-Ulloa, Jorge Vázquez-García, Sara Relaño, Tamara Hermida-Gómez, Vanesa Balboa-Barreiro, Lucia Lourido-Salas, Valentina Calamia, Patricia Fernandez-Puente, Cristina Ruiz-Romero, Juan Fernández-Tajes, Carlos Vaamonde-García, María C de Andrés, Natividad Oreiro, Francisco J Blanco, Ignacio Rego-Perez
Journal: Annals of the Rheumatic Diseases (2023)

Objectives To identify mitochondrial DNA (mtDNA) genetic variants associated with the risk of rapid progression of knee osteoarthritis (OA) and to characterise their functional significance using a cellular model of transmitochondrial cybrids. Methods Three prospective cohorts contributed participants. The osteoarthritis initiative (OAI) included 1095 subjects, the Cohort Hip and Cohort Knee included 373 and 326 came from the PROspective Cohort of Osteoarthritis from A Coruña. mtDNA variants were screened in an initial subset of 450 subjects from the OAI by in-depth sequencing of mtDNA. A meta-analysis of the three cohorts was performed. A model of cybrids was constructed to study the functional consequences of harbouring the risk mtDNA variant by assessing: mtDNA copy number, mitochondrial biosynthesis, mitochondrial fission and fusion, mitochondrial reactive oxygen species (ROS), oxidative stress, autophagy and a whole transcriptome analysis by RNA-sequencing. Results mtDNA variant m.16519C is over-represented in rapid progressors (combined OR 1.546; 95% CI 1.163 to 2.054; p=0.0027). Cybrids with this variant show increased mtDNA copy number and decreased mitochondrial biosynthesis; they produce higher amounts of mitochondrial ROS, are less resistant to oxidative stress, show a lower expression of the mitochondrial fission-related gene fission mitochondrial 1 and an impairment of autophagic flux. In addition, its presence modulates the transcriptome of cybrids, especially in terms of inflammation, where interleukin 6 emerges as one of the most differentially expressed genes. Conclusions The presence of the mtDNA variant m.16519C increases the risk of rapid progression of knee OA. Among the most modulated biological processes associated with this variant, inflammation and negative regulation of cellular process stand out. The design of therapies based on the maintenance of mitochondrial function is recommended.
Infographic. Aspetar clinical practice guideline on rehabilitation after ACL reconstruction: an interactive figure
Authors: Roula Kotsifaki, Vasileios Korakakis, Enda King, Olivia Barbosa, Dustin Maree, Michail Pantouveris, Andreas Bjerregaard, Julius Luomajoki, Jan Wilhelmsen, Rod Whiteley
Journal: British Journal of Sports Medicine (2023)

InfographicThis infographic interactively summarises the recommendations derived from the Aspetar clinical practice guideline on rehabilitation after anterior cruciate ligament reconstruction (ACLR). 1 The recommendations can be used by patients, clinicians, researchers and healthcare decision makers as a simple way of knowing the evidence for the effectiveness of interventions during rehabilitation after ACLR and the return to activities criteria.The guideline was developed in accordance with the Appraisal of Guidelines forREsearch & Evaluation (AGREE II) instrument and used the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach.A guideline development group systematically reviewed evidence from randomised clinical trials and systematic reviews to evaluate the effectiveness of rehabilitation interventions and guide clinicians and patients on the content of the optimal rehabilitation protocol after ACLR.The guideline highlights several new elements of ACLR management such as: exercise initiation, eccentric training, plyometrics training, and cross education which complement a recent systematic review 2 and other existing guidelines. 3xercise interventions should be considered the mainstay of ACLR rehabilitation.Adding modalities in the early phase may allow earlier pain-free commencement of exercise rehabilitation.However, the evidence for some modalities is conflicting, and the adverse effects, as well as the cost and time, required probably outweigh any benefits.Return to running and return to training/activity are key milestones for rehabilitation after ACLR however there is no evidence on which progression or discharge criteria should be used. 4 5 We therefore propose return to running and return to sport criteria based on the current literature and our clinical expertise.While there is a very low level of certainty for most components of rehabilitation, most of the recommendations were agreed to by expert clinicians.These data may be used as the basis in developing care pathways for rehabilitation after ACLR.
The GAPDH redox switch safeguards reductive capacity and enables survival of stressed tumour cells
Authors: Deepti Talwar, Colin G. Miller, Justus Grossmann, Lukasz Szyrwiel, Torsten Schwecke, Vadim Demichev, Ana-Matea Mikecin Drazic, Anand Mayakonda, Pavlo Lutsik, Carmen Veith, Michael D. Milsom, Karin Müller-Decker, Michael Mülleder, Markus Ralser, Tobias P. Dick
Journal: Nature Metabolism (2023)

Abstract Glyceraldehyde 3-phosphate dehydrogenase (GAPDH) is known to contain an active-site cysteine residue undergoing oxidation in response to hydrogen peroxide, leading to rapid inactivation of the enzyme. Here we show that human and mouse cells expressing a GAPDH mutant lacking this redox switch retain catalytic activity but are unable to stimulate the oxidative pentose phosphate pathway and enhance their reductive capacity. Specifically, we find that anchorage-independent growth of cells and spheroids is limited by an elevation of endogenous peroxide levels and is largely dependent on a functional GAPDH redox switch. Likewise, tumour growth in vivo is limited by peroxide stress and suppressed when the GAPDH redox switch is disabled in tumour cells. The induction of additional intratumoural oxidative stress by chemo- or radiotherapy synergized with the deactivation of the GAPDH redox switch. Mice lacking the GAPDH redox switch exhibit altered fatty acid metabolism in kidney and heart, apparently in compensation for the lack of the redox switch. Together, our findings demonstrate the physiological and pathophysiological relevance of oxidative GAPDH inactivation in mammals.
Precise modulation of transcription factor levels identifies features underlying dosage sensitivity
Authors: Sahin Naqvi, Seungsoo Kim, Hanne Hoskens, Harold S. Matthews, Richard A. Spritz, Ophir D. Klein, Benedikt Hallgrímsson, Tomek Swigut, Peter Claes, Jonathan K. Pritchard, Joanna Wysocka
Journal: Nature Genetics (2023)

Transcriptional regulation exhibits extensive robustness, but human genetics indicates sensitivity to transcription factor (TF) dosage. Reconciling such observations requires quantitative studies of TF dosage effects at trait-relevant ranges, largely lacking so far. TFs play central roles in both normal-range and disease-associated variation in craniofacial morphology; we therefore developed an approach to precisely modulate TF levels in human facial progenitor cells and applied it to SOX9, a TF associated with craniofacial variation and disease (Pierre Robin sequence (PRS)). Most SOX9-dependent regulatory elements (REs) are buffered against small decreases in SOX9 dosage, but REs directly and primarily regulated by SOX9 show heightened sensitivity to SOX9 dosage; these RE responses partially predict gene expression responses. Sensitive REs and genes preferentially affect functional chondrogenesis and PRS-like craniofacial shape variation. We propose that such REs and genes underlie the sensitivity of specific phenotypes to TF dosage, while buffering of other genes leads to robust, nonlinear dosage-to-phenotype relationships.
Tumor inflammation-associated neurotoxicity
Authors: Jasia Mahdi, Jorg Dietrich, Karin Straathof, Claire Roddie, Brian J. Scott, Tom Belle Davidson, Laura M. Prolo, Tracy T. Batchelor, Cynthia J. Campen, Kara L. Davis, Juliane Gust, Michael Lim, Robbie G. Majzner, Julie R. Park, Sonia Partap, Sneha Ramakrishna, Rebecca Richards, Liora Schultz, Nicholas A. Vitanza, Leo D. Wang, Crystal L. Mackall, Michelle Monje
Journal: Nature Medicine (2023)
Activation of insulin-like growth factor-1 receptor (IGF-1R) promotes growth of colorectal cancer through triggering the MEX3A-mediated degradation of RIG-I
Authors: Qiaobo Xie, Yanyan Chu, Wenmin Yuan, Yanan Li, Keqin Li, Xinfeng Wu, Xiaohui Liu, Rui Xu, Shuxiang Cui, Xianjun Qu
Journal: Acta Pharmaceutica Sinica B (2023)

Insulin-like growth factor-1 receptor (IGF-1R) has been made an attractive anticancer target due to its overexpression in cancers. However, targeting it has often produced the disappointing results as the role played by cross talk with numerous downstream signalings. Here, we report a disobliging IGF-1R signaling which promotes growth of cancer through triggering the E3 ubiquitin ligase MEX3A-mediated degradation of RIG-I. The active β-arrestin-2 scaffolds this disobliging signaling to talk with MEX3A. In response to ligands, IGF-1Rβ activated the basal βarr2 into its active state by phosphorylating the interdomain domain on Tyr64 and Tyr250, opening the middle loop (Leu130‒Cys141) to the RING domain of MEX3A through the conformational changes of βarr2. The models of βarr2/IGF-1Rβ and βarr2/MEX3A could interpret the mechanism of the activated-IGF-1R in triggering degradation of RIG-I. The assay of the mutants βarr2Y64A and βarr2Y250A further confirmed the role of these two Tyr residues of the interlobe in mediating the talk between IGF-1Rβ and the RING domain of MEX3A. The truncated-βarr2 and the peptide ATQAIRIF, which mimicked the RING domain of MEX3A could prevent the formation of βarr2/IGF-1Rβ and βarr2/MEX3A complexes, thus blocking the IGF-1R-triggered RIG-I degradation. Degradation of RIG-I resulted in the suppression of the IFN-I-associated immune cells in the TME due to the blockade of the RIG-I-MAVS-IFN-I pathway. Poly(I:C) could reverse anti-PD-L1 insensitivity by recovery of RIG-I. In summary, we revealed a disobliging IGF-1R signaling by which IGF-1Rβ promoted cancer growth through triggering the MEX3A-mediated degradation of RIG-I.
γ-Protocadherins control synapse formation and peripheral branching of touch sensory neurons
Authors: Shan Meltzer, Katelyn C. Boulanger, Anda M. Chirila, Emmanuella Osei-Asante, Michelle DeLisle, Qiyu Zhang, Brian T. Kalish, Aniqa Tasnim, Erica L. Huey, Leah C. Fuller, Erin K. Flaherty, Tom Maniatis, Andrew M. Garrett, Joshua A. Weiner, David D. Ginty
Journal: Neuron (2023)

Light touch sensation begins with activation of low-threshold mechanoreceptor (LTMR) endings in the skin and propagation of their signals to the spinal cord and brainstem. We found that the clustered protocadherin gamma (Pcdhg) gene locus, which encodes 22 cell-surface homophilic binding proteins, is required in somatosensory neurons for normal behavioral reactivity to a range of tactile stimuli. Developmentally, distinct Pcdhg isoforms mediate LTMR synapse formation through neuron-neuron interactions and peripheral axonal branching through neuron-glia interactions. The Pcdhgc3 isoform mediates homophilic interactions between sensory axons and spinal cord neurons to promote synapse formation in vivo and is sufficient to induce postsynaptic specializations in vitro. Moreover, loss of Pcdhgs and somatosensory synaptic inputs to the dorsal horn leads to fewer corticospinal synapses on dorsal horn neurons. These findings reveal essential roles for Pcdhg isoform diversity in somatosensory neuron synapse formation, peripheral axonal branching, and stepwise assembly of central mechanosensory circuitry.
Amplification is the primary mode of gene-by-sex interaction in complex human traits
Authors: Carrie Zhu, Matthew J. Ming, Jared M. Cole, Michael D. Edge, Mark Kirkpatrick, Arbel Harpak
Journal: Cell Genomics (2023)

Sex differences in complex traits are suspected to be in part due to widespread gene-by-sex interactions (GxSex), but empirical evidence has been elusive. Here, we infer the mixture of ways in which polygenic effects on physiological traits covary between males and females. We find that GxSex is pervasive but acts primarily through systematic sex differences in the magnitude of many genetic effects ("amplification") rather than in the identity of causal variants. Amplification patterns account for sex differences in trait variance. In some cases, testosterone may mediate amplification. Finally, we develop a population-genetic test linking GxSex to contemporary natural selection and find evidence of sexually antagonistic selection on variants affecting testosterone levels. Our results suggest that amplification of polygenic effects is a common mode of GxSex that may contribute to sex differences and fuel their evolution.
Identifying modifiable factors and their joint effect on dementia risk in the UK Biobank
Authors: Yi Zhang, Shi-Dong Chen, Yue-Ting Deng, Jia You, Xiao-Yu He, Xin-Rui Wu, Bang-Sheng Wu, Liu Yang, Ya-Ru Zhang, Kevin Kuo, Jian-Feng Feng, Wei Cheng, John Suckling, A. David Smith, Jin-Tai Yu
Journal: Nature Human Behaviour (2023)
m6A epitranscriptomic regulation of tissue homeostasis during primate aging
Authors: Zeming Wu, Mingming Lu, Di Liu, Yue Shi, Jie Ren, Si Wang, Ying Jing, Sheng Zhang, Qian Zhao, Hongyu Li, Zihui Yu, Zunpeng Liu, Shijia Bi, Tuo Wei, Yun-Gui Yang, Jingfa Xiao, Juan Carlos Izpisua Belmonte, Jing Qu, Weiqi Zhang, Weimin Ci, Guang-Hui Liu
Journal: Nature Aging (2023)
Long-term tolerance to skin commensals is established neonatally through a specialized dendritic cell subgroup
Authors: Antonin Weckel, Miqdad O. Dhariwala, Kevin Ly, Victoria M. Tran, Oluwasunmisola T. Ojewumi, Julianne B. Riggs, Jeanmarie R. Gonzalez, Laura R. Dwyer, Joy N. Okoro, John M. Leech, Margot S. Bacino, Grace D. Cho, Geil Merana, Niroshana Anandasabapathy, Yosuke Kumamoto, Tiffany C. Scharschmidt
Journal: Immunity (2023)
An industry built on harm
Authors: Juliet Dobson
Journal: BMJ (2023)

An industry built on harm Juliet Dobson managing editorEvery year, it has been estimated, up to around 500 suicides in England are linked to gambling (doi:10.1136/bmj.p766). 1 That would mean more than one person dying every day on average as a result of a preventable harm.Gambling related harms are pervasive, affecting not only people with gambling addictions but their family, friends, and wider society.More harmful, high risk gambling is associated with deprivation and unemployment, exacerbating existing health inequalities.